The main goal of this research is to determine whether a protein(s) specific for pancreatic carcinoma is present in serum samples obtained from patients with this disease. Previous attempts to detect such a protein in this laboratory by immunological techniques, including production of cancer specific antisera through the use of fetal pancreas extract of pancreatic cancer tissue, have been unsuccessful. We have therefore turned our attention to the detection of a protein specific for pancreatic cancer in patient sera by the two dimensional gel electrophoresis procedure developed by O'Farrell (J. Biol. Chem. 250, 4007, 1975). Several methods for enhancing the sensitivity and resolving power of this technique or the detection of minor proteins in serum or plasma are currently being evaluated, including selective removal of albumin, a sensitive silver staining procedure, and detection of proteins by autoradiography after labeling by reductive methylation of lysine residues with 14C-formaldehyde. It is expected that the optimized method will be capable of detecting protein spots at an abundance of 10 to the minus 2 power to 10 to the minus 3 power percent of total protein. O'Farrell has previously demonstrated that two dimensional gel electrophoresis can resolve 1100 distinct protein spots in a bacterial cell extract. The technique will be applied to the screening of sera from patients with pancreatic cancer and normal controls in an attempt to detect qualitative changes in the protein pattern that are specific for pancreatic cancer. The need for early diagnosis of carcinoma of the pancreas is great and we believe that the accomplishment of the goals of this research might eventually lead to a significant breakthrough in improving resectability and survival rate.